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Infect Immun. 2018 Oct 1. pii: IAI.00709-18. doi: 10.1128/IAI.00709-18. [Epub ahead of print]

Polymorphisms in receptors involved in opsonic and non-opsonic phagocytosis and the risk of infection in oncohematological patients.

Author information

1
Instituto de Biología y Genética Molecular, CSIC-Universidad de Valladolid, Valladolid, Spain.
2
Servicio de Hematología, Hospital Universitario Río-Hortega, Valladolid, Spain.
3
Servicio de Hematología, Hospital Clínico Universitario de Valladolid, Valladolid, Spain.
4
Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.
5
Departamento de Hematología, Hospital Universitario de Salamanca, Salamanca, Spain.
6
Centro de Investigación del Cáncer, Universidad de Salamanca, Campus Miguel de Unamuno, 37007, Salamanca, Spain.
7
Servicio de Microbiología, Hospital Universitario Río-Hortega, Valladolid, Spain.
8
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Valladolid, Valladolid, Spain.
9
Instituto de Biología y Genética Molecular, CSIC-Universidad de Valladolid, Valladolid, Spain mscres@ibgm.uva.es.

Abstract

High-risk hematologic malignancies are a privileged setting for infection by opportunistic microbes, invasive mycoses being one of the most serious complications. Recently, the genetic background has emerged as an unanticipated risk factor. For this reason, polymorphisms for genes encoding archetypal receptors involved in the opsonic and non-opsonic clearance of microbes, pentraxin-3, and Dectin-1, respectively, were studied and correlated with the risk of infection. Fungal, bacterial, and viral infections were registered in a group of 198 patients with high-risk hematologic malignancies. Polymorphisms for pentraxin-3 gene (PTX3) showed a significant association with the risk of fungal infection by Candida spp and, especially, by Aspergillus spp. This link remained even in patients undergoing antifungal prophylaxis, thus demonstrating the clinical relevance of PTX3 in the defense against fungi. CLEC7A polymorphisms did not show any definite correlation with the risk of invasive mycosis nor did they influence the expression of Dectin-1 isoforms generated by alternative splicing. PTX3 mRNA expression was significantly lower in samples from healthy volunteers who showed the polymorphisms, although not differences were observed in the extent of the induction elicited by bacterial lipopolysaccharide and heat-killed C. albicans, thus suggesting that the expression of PTX3 at the start of infection may influence the clinical outcome. PTX3 mRNA expression can be a good biomarker to establish proper antifungal prophylaxis in immunodepressed patients.

PMID:
30275011
DOI:
10.1128/IAI.00709-18

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